For clinical and theoretical purposes it appears important to study certain puzzling aspects of the metabolic fate of chlorpromazine, a drug administered chronically and often in high doses to many thousands of patients. When attempting to ascertain the total combined excretion of drug-related material in urine and feces of Rhesus monkey, it was found that 96% to 98% of tritium-labeled chlorpromazine was excreted during a period of 2 to 3 weeks. This extent of excretion is considerably higher than corresponding chemical or chromatographic assays have indicated. The discrepancy could be due to 1) excessive values by radioquantitation caused by tritium exchange, or 2) incomplete demonstration of all chlorpromazine metabolites by the assay procedures currently used. Both possibilities will be studied: 1) Tritium exchange will be proved or disproved by the use of C14-chlorpromazine as the tracer material, and 2) incomplete assay procedures will be improved by correlating C14-radioactivity on e.g. TLC plates with various analytical procedures. These will comprise TLC, using densitometry for recognizable chlorpromazine derivatives, detection, isolation and characterization of unknown chlorpromazine derivatives by NMR, GC/MS, and multiple-ion mass fragmentography--a new and promising technique--as well as by combinations of these and other conventional analytical methods. New methodology derived from the initial phase of the study will be applied to other representative tricyclic psychoactive drugs, i.e. phenothiazines with different side-chains and ring-substituents and structurally related compounds derived e.g. from imipramine, amitriptyline, thioxanthene and acridine.